An archaeal nucleoid-associated protein binds an essential motif in DNA replication origins

Abstract DNA replication typically has defined start sites, or replication origins, which are designated by their recognition by specific initiator proteins. In addition to initiators, general chromatin or nucleoid-associated proteins have been shown to play roles in modulating origin efficiency in...

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Main Authors: Rajkumar Dhanaraju, Rachel Y. Samson, Xu Feng, Alessandro Costa, Giovanni Gonzalez-Gutierrez, Stephen D. Bell
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60618-3
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author Rajkumar Dhanaraju
Rachel Y. Samson
Xu Feng
Alessandro Costa
Giovanni Gonzalez-Gutierrez
Stephen D. Bell
author_facet Rajkumar Dhanaraju
Rachel Y. Samson
Xu Feng
Alessandro Costa
Giovanni Gonzalez-Gutierrez
Stephen D. Bell
author_sort Rajkumar Dhanaraju
collection DOAJ
description Abstract DNA replication typically has defined start sites, or replication origins, which are designated by their recognition by specific initiator proteins. In addition to initiators, general chromatin or nucleoid-associated proteins have been shown to play roles in modulating origin efficiency in eukaryotes and bacteria. The role of chromatin proteins in origin function in the archaeal domain of life is poorly understood. Here, we describe a dissection of sequences elements required for in vivo function of an archaeal DNA replication origin. Our data reveal a hitherto uncharacterized sequence element, the ucm, is required for origin activity. We identify a protein, UBP, that interacts with the ucm and additionally with hundreds of other sites on the genome. We solve the crystal structure of UBP alone and in complex with ucm DNA, and further show that UBP interacts with the MCM replicative helicase. Taken together, our data provide evidence that UBP functions as a general nucleoid-associated protein that plays a key role in facilitating the egress of the MCM replicative helicase from DNA replication origins.
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spelling doaj-art-03279491f45a41b4910fc3f0f5e55bc32025-08-20T02:05:41ZengNature PortfolioNature Communications2041-17232025-06-0116111610.1038/s41467-025-60618-3An archaeal nucleoid-associated protein binds an essential motif in DNA replication originsRajkumar Dhanaraju0Rachel Y. Samson1Xu Feng2Alessandro Costa3Giovanni Gonzalez-Gutierrez4Stephen D. Bell5Department of Molecular and Cellular Biochemistry, Indiana University, Simon Hall MSB1Department of Molecular and Cellular Biochemistry, Indiana University, Simon Hall MSB1Department of Molecular and Cellular Biochemistry, Indiana University, Simon Hall MSB1Sir William Dunn School of PathologyDepartment of Molecular and Cellular Biochemistry, Indiana University, Simon Hall MSB1Department of Molecular and Cellular Biochemistry, Indiana University, Simon Hall MSB1Abstract DNA replication typically has defined start sites, or replication origins, which are designated by their recognition by specific initiator proteins. In addition to initiators, general chromatin or nucleoid-associated proteins have been shown to play roles in modulating origin efficiency in eukaryotes and bacteria. The role of chromatin proteins in origin function in the archaeal domain of life is poorly understood. Here, we describe a dissection of sequences elements required for in vivo function of an archaeal DNA replication origin. Our data reveal a hitherto uncharacterized sequence element, the ucm, is required for origin activity. We identify a protein, UBP, that interacts with the ucm and additionally with hundreds of other sites on the genome. We solve the crystal structure of UBP alone and in complex with ucm DNA, and further show that UBP interacts with the MCM replicative helicase. Taken together, our data provide evidence that UBP functions as a general nucleoid-associated protein that plays a key role in facilitating the egress of the MCM replicative helicase from DNA replication origins.https://doi.org/10.1038/s41467-025-60618-3
spellingShingle Rajkumar Dhanaraju
Rachel Y. Samson
Xu Feng
Alessandro Costa
Giovanni Gonzalez-Gutierrez
Stephen D. Bell
An archaeal nucleoid-associated protein binds an essential motif in DNA replication origins
Nature Communications
title An archaeal nucleoid-associated protein binds an essential motif in DNA replication origins
title_full An archaeal nucleoid-associated protein binds an essential motif in DNA replication origins
title_fullStr An archaeal nucleoid-associated protein binds an essential motif in DNA replication origins
title_full_unstemmed An archaeal nucleoid-associated protein binds an essential motif in DNA replication origins
title_short An archaeal nucleoid-associated protein binds an essential motif in DNA replication origins
title_sort archaeal nucleoid associated protein binds an essential motif in dna replication origins
url https://doi.org/10.1038/s41467-025-60618-3
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